Trifluoroacetic acid → 4-(((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-3-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-2-oxooxazolidin-5-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid

HRID 513902Notes

Reaction equation

HRID 513902 reaction equation
[CH3:1][C:2]([CH3:60])([CH2:10][C:11]([O:13][C@H:14]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C@@H:16]([CH2:17][CH2:18][C@:19]3([CH3:57])[C@@H:28]2[CH2:27][CH2:26][C@H:25]2[C@@:20]3([CH3:56])[CH2:21][CH2:22][C@@:23]3([C@@H:40]4[O:44][C:43](=[O:45])[N:42]([C:46]5([C:49]6[N:54]=[CH:53][C:52]([Cl:55])=[CH:51][N:50]=6)[CH2:48][CH2:47]5)[CH2:41]4)[CH2:35][C:34](=[O:36])[C:33]([CH:37]([CH3:39])[CH3:38])=[C:24]32)[C:15]1([CH3:59])[CH3:58])=[O:12])[C:3]([O:5]C(C)(C)C)=[O:4].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:55][C:52]1[CH:51]=[N:50][C:49]([C:46]2([N:42]3[CH2:41][C@H:40]([C@:23]45[CH2:35][C:34](=[O:36])[C:33]([CH:37]([CH3:38])[CH3:39])=[C:24]4[C@@H:25]4[C@@:20]([CH3:56])([CH2:21][CH2:22]5)[C@@:19]5([CH3:57])[C@@H:28]([C@:29]6([CH3:32])[C@@H:16]([CH2:17][CH2:18]5)[C:15]([CH3:58])([CH3:59])[C@@H:14]([O:13][C:11](=[O:12])[CH2:10][C:2]([CH3:1])([CH3:60])[C:3]([OH:5])=[O:4])[CH2:31][CH2:30]6)[CH2:27][CH2:26]4)[O:44][C:43]3=[O:45])[CH2:48][CH2:47]2)=[N:54][CH:53]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866903971-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-3-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-2-oxooxazolidin-5-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate

Product 1

HCID 866903994-(((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-3-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-2-oxooxazolidin-5-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acidYield 67.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-3-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-2-oxooxazolidin-5-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate (109) (80 mg, 0.094 mmol) in DCM (10 mL) was added TFA (1 mL, 0.094 mmol). The reaction mixture was stirred at rt overnight, then diluted with DCM (20 ml) and washed with water (2×15 ml), saturated sodium bicarbonate solution (20 ml) and brine (20 ml), dried over sodium sulfate, filtered and concentrated to get a residue. The residue was purified on silica gel using petroleum ether/EtOAc (4:1 to 1:1) as eluent to give the product 4-(((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-3-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-2-oxooxazolidin-5-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid (111) (50 mg, 67%) as a white solid. This material was lyophilized to give a white powder. Stereochemistry was tentatively assigned as drawn but not fully confirmed spectroscopically. 1H NMR (400 MHz, CHLOROFORM-d) δ=8.58 (s, 2H), 5.04 (t, J=8.5 Hz, 1H), 4.51 (dd, J=4.6, 10.9 Hz, 1H), 3.41-3.04 (m, 4H), 2.75-2.44 (m, 3H), 2.36 (d, J=13.3 Hz, 1H), 2.12-0.72 (m, 49H); LC/MS: m/z calculated 791.4. found 792.3 (M+1)+.

Workup

  1. washwashed with water (2×15 ml), saturated sodium bicarbonate solution (20 ml) and brine (20 ml)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto get a residue
  6. customThe residue was purified on silica gel

Sources & evidence

ORD record
ord-e95168d51a6e4ac89ee2709d37146eef
Source dataset
uspto-grants-2015_08
Patent number
US09102685B2

Reaction notes

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